BREFELDIN-A, G-PROTEINS AND GOLGI MEMBRAN E-TRANSPORT

This review has attempted to provide a synthesis of the growing number of observations on the effects of the fungal metabolite brefeldin A. This drug dramatically alters the morphology of the Golgi complex and the return of Golgi markers to the endoplasmic reticulum. Intercistern al transport in the Golgi complex is mediated by non clathrin coated v esicles, The formation of these vesicles is dependent on the recruitme nt of a set of proteins from the cytosol, the coatomer. Brefeldin A bl ocks this step as demonstrated by the redistribution of beta-COP, a co mponent of coatomer, from Golgi to cytosol. In the absence of vesicle formation, Golgi cisternae tend to form tubules which are elongated al ong microtubules and rapidly fuse with the endoplasmic reticulum. Sinc e all of these changes can be prevented by pretreating intact or perme abilized cells with AlF4- or GTPgammaS respectively (both of which are thought to act by locking G proteins in the active state), the potent ial role of trimeric G protein and small G protein has been investigat ed. Current data suggest that the assembly of cytosolic proteins on an d off Golgi membranes is a process controlled in part by one or more m embrane bound trimeric G proteins and by ARF small G protein family me mbers. Binding of ARF to Golgi membranes is necessary before coatomer can bind these membranes, so the primary effect of BFA seems to be on the reaction responsible for ARF binding. The recent discovery that Go lgi membrane can specifically catalyse the exchange of GTP onto ARF an d that BFA prevents this function have confirmed this hypothesis.